Gene Mutation And Expression Of SH3BP2 In Cherubism

Cherubism disease,also known as familial fibrous dysplasia of jaws,is a rare benign,self-limiting polycystic disease.The disease,at present is considered to be an autosomal dominant genetic disease which often has familial tendency.Cherubism not only cause patients with severe facial deformities,but also serious effect on the patient's alveolar development.Currently,the pathogenicity gene of the disease has been located in chromosome region 4p16.3 between regions of D4S127 and D4S115 markers,furthermore the gene SH3BP2 in this zone is identified to be the pathogenicity candidate gene of cherubism.The gene missense point mutation at the molecular level leads to the disease.At the same time,multinucleated osteoclast-like cells are characteristic cells in cherubism lesions,which have close relationship with the clinical and pathological manifestations of such disease.Objective The purpose of this study is to detect the mutation and expression of SH3BP2 in Chinese patients of cherubism and to detect the gene mutation and mutation type of SH3BP2 in Chinese patients,also to investigate the possible relationship of gene mutation and multinucleated giant cells in lesions.Therefore,it is conducive to further revealing the etiolog of cherubism,and providing some foundations for the gene diagnosis,treatment,and prevention of the disease in the future.Methods Genomic DNA was extracted from paraffin-embedding tissues and peripheral blood samples from 10 cases of cherubism(6 familial cherubisms and 4 sporadic cherubisms).SH3BP2 mutations were detected by PCR-direct sequencing. The nature of multinucleated giant cells in lesions was detected by immunohistochemical staining using paraffin-embedding tissues sections.The SH3BP2 protein was detected by immunohistochemical staining.Results 3 missense mutaions(G1520A,G1505A,G1505C) in exon 9 of SH3BP2 were identified which led to 3 transitions(Gly420Glu,Arg415Gln, Arg415Pro).There are not any abnormalities in exon 3 of SH3BP2 except of 1 case which had not PCR products.The protein SH3BP2 and the calcitonin receptor were detected in the cytoplasm of all multinucleated giant cells and parts of monocaryon matrix cells in 8 paraffin-embedding samples.Conclusions In Chinese population,gene mutations of cherubism disease are mainly concentrated in the exon 9 of SH3BP2 gene,and the SH3BP2 gene mutation may participate in the differentiation and maturation of multinucleated osteoclast-like cells in the lesion of cherubism,but the definit mechanism is yet to be clarified.